Exogenous Ketones for Obesity

Overseen By Sarah Purcell, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Appetite suppressants, Sleep aids

Disqualifiers: Cardiovascular, Diabetes, Cancer, Thyroid, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an exogenous ketone supplement can help manage appetite in adults with obesity. Researchers aim to determine if these supplements can influence hunger and fullness hormones, aligning them more closely with those in individuals without obesity. Participants will take the supplement and a placebo on different days, with their appetite and food intake measured. This trial is suitable for adults who are not very active, have a body mass index (BMI) between 18.5 and 40, and do not have major health conditions such as diabetes or heart disease. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on appetite management.

Will I have to stop taking my current medications?

The trial requires that participants do not use any regular medication or supplement that may affect appetite, energy balance, or sleep. If you are starting any new prescription medication, you must do so at least two weeks before the first study day visit and not during the study.

Is there any evidence suggesting that exogenous ketones are likely to be safe for humans?

Research has shown that taking exogenous ketones is safe and generally well-tolerated. These supplements raise levels of beta-hydroxybutyrate (BHB) in the blood and are considered safe for healthy individuals. One study found that a specific type of exogenous ketones was safe for healthy teenagers, indicating that serious side effects are uncommon in these groups.

Regarding side effects, studies report mostly positive results, with no major negative effects linked to the supplement. This is encouraging for those considering participation in a clinical trial involving exogenous ketones. While researchers continue to study the effects on individuals with obesity, current data from healthy participants suggests a promising safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for obesity, which often include lifestyle interventions, medications, or even surgery, exogenous ketones offer a unique approach by supplementing the body with ketones directly. These supplements can quickly elevate blood ketone levels, potentially boosting fat metabolism and energy expenditure without the need for a ketogenic diet. Researchers are excited about exogenous ketones because they might provide faster and more sustained weight management benefits compared to current options, with potentially fewer side effects. This innovative approach could revolutionize how obesity is managed, offering a simpler and more flexible option for those struggling with weight loss.

What evidence suggests that exogenous ketones might be an effective treatment for obesity?

Research has shown that exogenous ketones, which participants in this trial may receive, can raise blood ketone levels. Ketones help the body produce energy. These supplements can boost ketosis, a state where the body burns fat for energy instead of carbohydrates. This shift in energy source may help control appetite, possibly leading to weight loss. Previous studies found that exogenous ketones can affect hunger hormones like ghrelin and GLP-1, which regulate feelings of hunger and fullness. This suggests that exogenous ketones might help individuals with obesity manage their appetite similarly to those without obesity. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for young and middle-aged adults with obesity who are healthy otherwise. They should be interested in how a ketone supplement might affect their appetite, energy use, and eating habits compared to a placebo. Participants will need to commit to several study visits and follow specific dietary instructions.

Inclusion Criteria

Not currently pregnant or lactating, not planning to become pregnant in the next 12 weeks

Body mass index (BMI): 18.5 - 40.0 kg/m2

Ability and willingness to fast for 12 hours before each study day visit

Exclusion Criteria

I have or had major health issues like heart disease, diabetes, cancer, thyroid problems, HIV, hepatitis B or C, kidney or liver diseases, or polycystic ovary syndrome.

I have untreated conditions like high blood pressure or sleep problems that could affect my appetite or energy.

Currently or in the past six months: use of regular medication or supplement that may affect appetite, energy balance, or sleep, regular use of tobacco or nicotine products, starting any new prescription medication within two weeks of the first study day visit or during the study, working night shifts or traveling across more than 2 time zones within two weeks of and throughout the study, food intolerances or allergies that cannot be accommodated, history of surgical procedure for weight loss at any time (e.g., gastroplasty, gastric bypass, gastrectomy or partial gastrectomy, adjustable banding, gastric sleeve); history of extensive bowel resection for other reasons, current alcohol or substance abuse (score >2 on the cut down-annoyed-guilty-eye opener [CAGE] questionnaire), current or past history of eating disorders including anorexia nervosa, bulimia, binge eating disorder (self-report or score >20 on the Eating Attitudes Test - 26 [EATS-26] questionnaire), weight loss >5% in past 12 weeks for any reason

Timeline for a Trial Participant

Screening and Baseline

Participants are screened for eligibility to participate in the trial

1 hour

1 visit (in-person)

Run-in Diet

Participants follow a 1-day energy-balanced run-in diet to ensure energy balance and weight maintenance prior to each study day

1 day

Study Visit Days

Participants undergo two 4.5-hour study visits, one with the exogenous ketone supplement and one with placebo, including metabolic rate tests, appetite ratings, and blood sample collections

4.5-5 hours per visit

2 visits (in-person)

Post-study Day Dietary Intake Assessment

Participants are provided with 1.5 days of meals and snacks to assess free-living ad libitum dietary intake

1.5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Exogenous Ketones

Trial Overview

The study tests if exogenous ketones can change appetite hormones in obese individuals to resemble those without obesity. It's a randomized single-blind crossover study where participants take a ketone ester or placebo on different days, followed by measuring hunger ratings, hormone levels, energy expenditure, and food intake.

How Is the Trial Designed?

Group I: Ketone supplement condition second Experimental Treatment 1 Intervention

Group II: Ketone supplement condition first Experimental Treatment 1 Intervention

Exogenous Ketones is already approved in United States, European Union for the following indications:

Approved in United States as Exogenous Ketones for:

• General Health and Wellness
• Appetite Suppression

Approved in European Union as Exogenous Ketones for:

• General Health and Wellness
• Appetite Suppression

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

A one-day ketogenic diet significantly increased total energy expenditure by about 110 calories compared to an isocaloric control diet, suggesting it may help with energy balance.

Supplementation with exogenous ketone salts did not enhance energy expenditure or appetite regulation compared to the isocaloric control diet, indicating that they may not provide additional benefits in energy balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants. Hägele, FA., Dörner, R., Koop, J., et al.[2023]

In a randomized controlled trial with 18 adults with prediabetes, a ketone monoester (KEβHB) supplement significantly lowered plasma glucose levels compared to a placebo, indicating its potential for managing blood sugar in at-risk individuals.

The KEβHB supplement also increased levels of insulin and other glucoregulatory peptides, suggesting a mechanism by which it may help improve glucose control in prediabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial. Bharmal, SH., Cho, J., Alarcon Ramos, GC., et al.[2023]

In a study involving 18 adults with prediabetes, ingestion of the ketone monoester β-hydroxybutyrate (KEβHB) significantly elevated blood ketone levels and resulted in lower levels of remnant cholesterol and triglycerides, indicating potential cardiovascular benefits.

The positive effects on lipid profile were more pronounced in individuals with higher habitual saturated fat intake, suggesting that KEβHB may be particularly beneficial for those at risk of cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial. Liu, Y., Bharmal, SH., Kimita, W., et al.[2022]

A study involving 24 healthy adults showed that consuming a ketone monoester three times a day for 28 days safely elevated blood ketone levels without affecting body weight, blood glucose, cholesterol, or kidney function.

The only reported side effect was mild nausea in a small number of instances, indicating that the ketone monoester is well-tolerated for sustained use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Soto-Mota, A., Vansant, H., Evans, RD., et al.[2020]

A hypocaloric ketogenic diet (KD) significantly increased levels of beta-hydroxybutyrate (BHB) in participants, and this effect was enhanced by the addition of exogenous ketone salts (KS), leading to a 26% increase in ketonemia compared to a placebo.

The combination of the KD and KS not only augmented ketonemia but also resulted in a 6% reduction in fasting glucose levels, suggesting that the hypoglycemic effects of a ketogenic diet may be further improved with exogenous ketones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts. Buga, A., Kackley, ML., Crabtree, CD., et al.[2023]

In a study involving 14 adults with obesity, 14 days of β-hydroxybutyrate (β-OHB) supplementation significantly improved cerebral blood flow and cognition, suggesting potential benefits for brain health in this population.

While β-OHB supplementation enhanced cognitive performance and cerebrovascular outcomes, it did not affect levels of brain-derived neurotrophic factor (BDNF), indicating that the cognitive improvements may be primarily due to increased blood flow rather than changes in BDNF levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial. Walsh, JJ., Caldwell, HG., Neudorf, H., et al.[2022]

Ketone bodies, particularly β-hydroxybutyrate (BOHB) and acetone, can significantly increase in concentration during certain diseases or therapeutic interventions, providing valuable metabolic insights for managing conditions like heart failure and obesity-related diseases.

Monitoring ketone body levels can help optimize weight loss strategies and improve disease management by promoting the use of ketones as an alternative fuel source when glucose utilization is impaired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis. Anderson, JC., Mattar, SG., Greenway, FL., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12113729/

Effectiveness of Exogenous Ketone Salts in Enhancing ...

Our findings indicate that KS markedly increases plasma ketone body interconversion, presumably to supply peripheral tissues for ATP generation.

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1744388123000555

Effects of ketone supplements on blood β-hydroxybutyrate ...

The meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's ...

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physoc.onlinelibrary.wiley.com

physoc.onlinelibrary.wiley.com/doi/10.1113/EP090430

Exogenous ketone supplementation: an emerging tool for ...

Exogenous oral ketone supplements, primarily in form of ketone salts or esters, have emerged as a useful research tool for manipulating metabolism.

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nutrition.bmj.com

nutrition.bmj.com/content/early/2023/07/05/bmjnph-2023-000672

Evaluation of the safety and tolerability of exogenous ...

There are three thoroughly studied ketone supplements for inducing ketosis: ketone salts,15–17 ketone esters18 and medium-chain triglycerides.

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frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.618520/full

The Effects of a 6-Week Controlled, Hypocaloric Ketogenic ...

This study investigated the effects of daily exogenous ketone BHB supplementation (in the form of a racemic BHB salt) in the context of a 6-week ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11009516/

Evaluation of the safety and tolerability of exogenous ketosis ...

Free D-BHB was a safe and well-tolerated intervention for inducing sustained exogenous ketosis. Being bioidentical, salt-free and lacking intermediate ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2161831323000340

Effects of Exogenous Ketone Supplementation on Blood ...

The available evidence indicates that acute ingestion of exogenous ketones leads to increased blood BHB and decreased blood glucose.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8000900/

The Effect of Exogenous Beta-Hydroxybutyrate Salt ...

We conclude that supplementing with exogenous beta-hydroxybutyrate salts is safe and well-tolerated by healthy adolescents.

9.

medrxiv.org

medrxiv.org/content/10.1101/2023.06.12.23291298v1.full.pdf

HYDROXYBUTYRATE IN HEALTHY ADULT SUBJECTS

thoroughly studied ketone supplements for inducing ketosis: ketone salts [15–17], ketone. 63 esters [18], and medium-chain triglycerides [19].

10.

mdpi.com

mdpi.com/1424-8247/18/10/1436

Divergent Hepatic Outcomes of Chronic Ketone ...

Exogenous ketone supplementation has emerged as a novel nutritional intervention capable of rapidly elevating circulating levels of beta-hydroxybutyrate (BHB), ...